Journal of Neuroscience最新文献

Pitch and time are the essential dimensions defining musical melody. Recent electrophysiological studies have explored the neural encoding of musical pitch and time by leveraging probabilistic models of their sequences, but few have studied how the features might interact. This study examines these interactions by introducing "chimeric music," which pairs two distinct melodies, and exchanges their pitch contours and note onset-times to create two new melodies, distorting musical pattern while maintaining the marginal statistics of the original pieces' pitch and temporal sequences. Through this manipulation, we aimed to dissect the music processing and the interaction between pitch and time. Employing the temporal response function (TRF) framework, we analyzed the neural encoding of melodic expectation and musical downbeats in participants with varying levels of musical training. Our findings from 27 participants of either sex revealed differences in the encoding of melodic expectation between original and chimeric stimuli in both dimensions, with a significant impact of musical experience. This suggests that decoupling the pitch and temporal structure affects expectation processing. In our analysis of downbeat encoding, we found an enhanced neural response when participants heard a note that aligned with the downbeat during music listening. In chimeric music, responses to downbeats were larger when the note was also a downbeat in the original music that provided the pitch sequence, indicating an effect of pitch structure on beat perception. This study advances our understanding of the neural underpinnings of music, emphasizing the significance of pitch-time interaction in the neural encoding of music.Significance Statement Listening to music is a complex and multidimensional auditory experience. Recent studies have investigated the neural encoding of pitch and timing sequences in musical structure, but they have been studied independently. This study addresses the gap in understanding of how the interaction between pitch and time affects their encoding. By introducing "chimeric music," which decouples these two melodic dimensions, we investigate how this interaction influences the neural activities using EEG. Leveraging and the temporal response function (TRF) framework, we found that structural violations in pitch-time interactions impact musical expectation processing and beat perception. These results advance our knowledge of how the brain processes complex auditory stimuli like music, underscoring the critical role of pitch and time interactions in music perception.

N,N-dimethyltryptamine (DMT) is a serotonergic psychedelic that is being investigated clinically for the treatment of psychiatric disorders. Although the neurophysiological effects of DMT in humans are well-characterized, similar studies in animal models and data on the neurochemical effects of DMT are generally lacking, which are critical for mechanistic understanding. In the current study, we combined behavioral analysis, high-density (32-channel) electroencephalography, and ultra-high-performance liquid chromatography-tandem mass spectrometry to simultaneously quantify changes in behavior, cortical neural dynamics, and levels of 17 neurochemicals in medial prefrontal and somatosensory cortices before, during, and after intravenous administration of three different doses of DMT (0.75 mg/kg, 3.75 mg/kg, 7.5 mg/kg) in male and female adult rats. All three doses of DMT produced head twitch response with most twitches observed after the low dose. DMT caused dose-dependent increases in serotonin and dopamine levels in both cortical sites and a reduction in EEG spectral power in theta (4-10 Hz) and low gamma (25-55 Hz), and increase in spectral power in delta (1-4 Hz), medium gamma (65-115 ), and high gamma (125-155 Hz) bands. Functional connectivity decreased in the delta band and increased across the gamma bands. We detected cortical DMT in baseline wake condition in 80% of the animals tested at levels comparable to serotonin and dopamine, which together with a previous study in occipital cortex, motivates cross-species studies to confirm endogenous presence of DMT. This study represents one of the most comprehensive characterizations of psychedelic drug action in rats and the first to be conducted with DMT.Significance Statement N,N-dimethyltryptamine (DMT) is a serotonergic psychedelic with potential as a tool for probing the neurobiology of consciousness and as a therapeutic agent for psychiatric disorders. However, the neurochemical and neurophysiological effects of DMT in rat, a preferred animal model for mechanistic studies, are unclear. We demonstrate that intravenous DMT caused a dose-dependent increase in serotonin and dopamine in medial prefrontal and somatosensory cortices, and simultaneously increased gamma functional connectivity. Similar effects have been shown for other serotonergic and atypical psychedelics, suggesting a shared mechanism of drug action.

The brain can be conceptualized as a control system facilitating transitions between states, such as from rest to motor activity. Applying network control theory to measurements of brain signals enables characterization of brain dynamics through control properties. However,most prior studies that have applied network control theory have evaluated brain dynamics under unperturbed conditions, neglecting the critical role of external perturbations in accurate system identification. In this study, we combine a perturbation input paradigm with a network control theory framework and propose a novel method for estimating the controllability Gramian matrix in a simple, theoretically grounded manner. This method provides insights into brain dynamics, including overall controllability (quantified by the Gramian's eigenvalues) and specific controllable directions (represented by its eigen vectors). As a proof of concept, we applied our method to transcranialmagnetic stimulation-induced electroencephalographic responses across four motor-related states and two resting states. We found that states such as open-eye rest, closed-eye rest, and motor-related states were more effectively differentiated using controllable directions than overall controllability. However, certain states, like motor execution and motor imagery, remained indistinguishable using these measures. These findings indicate that some brain states differ in their intrinsic control properties as dynamical systems, while others share similarities. This study underscores the value of control theory-based analyses in quantitatively how intrinsic brain states shape the brain's responses to stimulation, providing deeper insights into the dynamic properties of these states. This methodology holds promise for diverse applications, including characterizing individual response variability and identifying conditions for optimal stimulation efficacy.Significant statement The brain can be viewed as a control system transitioning between states, such as from rest to motor activity. Previous studies using network control theory mostly evaluated brain dynamics without external perturbations, neglecting their role in accurate system identification. This study integrates perturbation inputs with network control 44 theory to propose a method for estimating the controllability Gramian, thereby providing insights into brain dynamics. We applied this approach to TMS-induced EEG responses in motor-related and resting states. Our findings show that controllable directions (eigenvectors) allow better discrimination between states than overall controllability. Our method can quantitatively assess brain state differences, and has potential applications in characterizing individual response variability and optimizing stimulation efficacy.

The central nervous system is characterized by its limited regenerative potential, yet striking examples of functional recovery after injury in animal models and humans highlight its capacity for repair. Little is known about repair of pathways/circuits after traumatic brain injury (TBI), which results in disruption of connectivity. Here we utilize a mouse model of diffuse traumatic axonal injury (Impact-acceleration TBI) in order to explore, for the first time, the evolution of structural and functional changes in the terminal fields of the injured visual system. Retinal ganglion cell (RGC) axons and synapses were genetically labeled via AAV transduction, while anterograde and transsynaptic tracers were used to mark terminals and postsynaptic cells. Functional connectivity and visual integrity were assessed by monitoring c-Fos expression following light stimulation and pattern-reversal visual evoked potentials (pVEPs). Our findings demonstrate that, although TAI results in approximately a 50% loss of RGC axons and terminals, surviving RGCs undergo collateral sprouting, a form of compensatory branching of surviving axons, that restores terminal density to pre-injury levels. Transsynaptic tracing and c-Fos mapping confirmed the reestablishment of connectivity, which was also associated with significant improvements in visual function as measured by pVEPs. Interestingly, the recovery process exhibited sexual dimorphism, with female mice showing delayed or incomplete repair. Moreover, collateral sprouting proceeded normally in Sarm1 knockout mice, evidence of some independence from Wallerian degeneration. Our findings show that collateral sprouting may be an important mechanism of circuit repair in TAI and may represent a promising target for therapeutic interventions.Significance Statement Homotypic collateral sprouting -the process by which uninjured axons from the same neuronal source extend new branches to reinnervate targets deprived of their original connections- is a fundamental yet understudied mechanism for CNS repair following injury. Unlike heterotypic sprouting, involving sprouting from unrelated pathways, homotypic sprouting offers potential to restore circuit architecture after partial lesions. Here, we employed a model of diffuse axonal injury in the mouse visual system to examine this mechanism. Our research demonstrates surviving retinal ganglion cell axons can re-establish terminal fields, achieving structural and functional connectivity. Importantly, we discovered significant sex differences: female mice showed delayed/incomplete recovery compared to males. These findings provide evidence of repair of brain circuits perturbed by TBI and the role of homotypic sprouting.